Vitamin E (Vit E) is a lipid soluble antioxidant which inhibits the peroxidation of membrane lipids. Several proposed hypotheses have linked free radical reactions to the etiology of aging, cancer, and atherosclerosis. Diets that are enriched in antioxidants have been suggested as one means of decreasing the morbidity and motality due to degenerative diseases and non-specific age changes. Physiologically, Vit E is transported in the body by plasma lipoproteins from which it readily transfers among lipoproteins and blood cells. The utilization of this vitamin is, necessarily, a function of its distribution, transport and reactivity. The specific aims of this proposal are (a) to determine the kinetics and mechanism of the transfer Vit E among lipoproteins and between lipoproteins and cells, (b) to examine the intermolecular interactions of Vit E with various phospholipids and to thereby identify specific interactions, if any, which could regulate the thermodynamics of its distribution, (c) to measure dose-response effects of Alpha-tocopherol with respect to inhibition of lipid peroxidation in model membrane systems, and (d) to verify these processes in a real membrane, i.e., the erythrocytes. With the completion of the above objectives one should have a better understanding of the role of this vitamin in maintenance of membrane structure and functional integrity. Additionally, it should help provide some guidance in the development of a rational basis for the use of Vit E as a therapeutic agent.